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1.
Oncologist ; 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33044751

RESUMO

Agents blocking BRAF and MEK produce robust responses in patients with BRAFV600 mutated melanoma, however more accurate clinical biomarkers are needed to predict prognosis. To explore this question, we retrospectively studied 158 patients with BRAF-mutated melanoma treated with BRAF +/- MEK inhibitors. We found that the number of distinct tumor sites upon initiation of targeted therapy is associated with decreased progression-free survival but had no effect on overall survival. Serum values of LDH and ALC/ANC ratio independently had the strongest association with both progression-free survival and overall survival. Using both of these markers can help stratify prognosis of patients with metastatic melanoma receiving targeted therapy.

2.
PLoS One ; 15(10): e0239736, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33002008

RESUMO

The identification of anammox bacteria is mostly relied on PCR with various marker genes. However, the community composition revealed by different marker genes and whether the marker genes influence the resulted community composition remain unclear. We compared the community structure of anammox bacteria in enriched and natural environments revealed by 16S rRNA and functional genes (hzo, hzsA and hzsB) from public database and published papers. The genus of Ca. Scalindua showed the lowest similarities with other genera, especially for the hzsA gene (66.9%-68.6%). The 16S rRNA gene is the most commonly used marker gene in natural habitats with 151 out 221 papers in total. The anammox bacterial community composition is distributed according to the source of habitat regardless the use of various marker genes. The role of marker gene is limited with explanatory of 5.4% for variance of community composition, versus 20.5% of habitat. The effect of marker gene is mainly acted on freshwater habitat, which shows significant different community composition revealed by 16S rRNA and hzo, with Ca. Brocadia and Ca. Jettenia as dominant genus, respectively.

3.
Bioorg Chem ; 104: 104319, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-33011531

RESUMO

The barks of Magnolia officinalis var. biloba, Magnoliae cortex, have been used as traditional Chinese medicines for several centuries. In this study, phytochemical investigation of M. officinalis var. biloba bark extract afforded five pairs of novel enantiomeric oligomeric neolignans, (±)-mooligomers A-E (1-5). (±)-1 and (±)-2 were two diastereomeric pairs of enantiomers with six C6-C3 subunits, and (±)-4 was a pair of previously unreported tetrameric neolignans bearing eight C6-C3 subunits. (±)-5 is the first example of a naturally occurring trilignan featuring an eight-membered ring with a magnolol moiety. The absolute configurations of (±)-1-(±)-5 were elucidated on the basis of HRESIMS, 1D and 2D NMR spectroscopy and electronic circular dichroism (ECD) calculations. Among the compounds tested for their PTP1B inhibitory activities, (±)-2, (±)-4 and (±)-5 displayed significant PTP1B inhibitory activities with IC50 values of 0.14-2.10 µM. Furthermore, a Molecular docking simulation of PTP1B and active compounds [(±)-2, (±)-4 and (±)-5] exhibited that these active compounds possess low binding affinities ranging from - 5.9 to - 7.7 kcal/mol.

4.
Chemistry ; 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-33084132

RESUMO

Developing high-efficiency bifunctional electrocatalysts toward hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) in alkaline surroundings is essential and challenging for generating clean hydrogen massively. Herein, a novel self-assembly two-dimensional (2D) NiO/CeO2 heterostructure (HS) consisted of NiO and CeO2 nanocrystals has been firstly prepared via a facile two-step approach and utilized as an enhanced bifunctional electrocatalyst for HER and OER under alkaline condition. It is concluded that 2D NiO/CeO2 HS rich in oxygen vacancies demonstrates attractive electrocatalytic properties for both HER and OER in 1 M KOH, including low onset overpotential (η1), η10 and Tafel slope, excellent durability as well as large active surface area. Owing to this, the self-assembly 2D NiO/CeO2 HS is believed to be an efficient bifunctional electrocatalyst toward HER and OER.

5.
J Cell Commun Signal ; 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33058043

RESUMO

Due to the steadily rising morbidity and mortality, thyroid cancer remains the most commonly seen endocrine cancer. The present study attempted to investigate the mechanism from the perspective of long non-coding RNA (lncRNA) regulation. We identified 53 markedly increased lncRNAs in thyroid cancer samples according to TCGA data. Among them, high lncRNA DIO3OS expression was a risk factor for thyroid cancer patients' poorer overall survival. DIO3OS showed to be considerably increased within thyroid cancer tissue samples and cells. Knocking down DIO3OS within thyroid carcinoma cells suppressed cancer cell viability, the capacity of DNA synthesis, cell invasion, as well as cell migration; besides, proliferating markers, ki-67 and PCNA, were decreased by DIO3OS knockdown. Cancer bioinformatics analysis suggested that NF-κB2 might be related to DIO3OS function in thyroid cancer carcinogenesis. NF-κB2 was positively correlated with DIO3OS, and DIO3OS knockdown decreased NF-κB2 protein levels. Knocking down NF-κB2 within thyroid carcinoma cells suppressed cancer cell viability, the capacity of DNA synthesis, cell invasion, cell migration, and the protein levels of proliferating markers. Let-7d directly targeted DIO3OS and NF-κB2; DIO3OS knockdown upregulated let-7d expression. The overexpression of let-7d suppressed cancer cell viability, the capacity of DNA synthesis, cell invasion, cell migration, as well as the protein levels of proliferating markers. Let-7d inhibition remarkably attenuated the functions of DIO3OS knockdown in NF-κB2 expression and thyroid cancer cell phenotype. In conclusion, DIO3OS/let-7d/NF-κB2 axis regulates the viability, DNA synthesis capacity, invasion, and migration of thyroid cancer cells. The clinical application of this axis needs further in vivo and clinical investigation.

6.
Coron Artery Dis ; 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33060524

RESUMO

OBJECTIVES: The purpose of this study was to evaluate the association of diabetes mellitus (DM) with neointimal formation after implantation of second-generation drug-eluting stent (DES) visualized by optical coherence tomography (OCT). METHODS: Patients with single de novo coronary artery disease treated with second-generation DES between June 2014 and June 2017 in our department underwent OCT examination at 1-year follow-up and were enrolled in this retrospective study. The primary end point was in-stent mean neointimal thickness (MNT), and secondary end points included uncovered stent strut, minimal lumen area (MLA), neointimal burden, neointimal hyperplasia (NIH) patterns and stent thrombosis (ST) after 1 year of OCT follow-up. RESULTS: A total of 68 patents with DM (DM group) and 216 patients without DM (non-DM group) were enrolled. At 1-year follow-up, the DM group compared with the non-DM group, showed: MNT [160 (85-245) µm vs. 120 (60-220) µm, P = 0.038] and neointimal burden [21.4 (8.3-30.1)% vs. 14.0 (5.7-26.1)%, P = 0.023] to be significantly increased. Concurrently, MLA [4.60 (3.53-6.06) mm vs. 5.76 (4.28-7.20) mm, P = 0. 0.002] was significantly reduced. Interestingly, the degree of uncovered struts (7.3 ± 7.1% vs. 7.7 ± 6.7%, P = 0.704), NIH patterns (P = 0.984), and ST (7.9% vs. 7.4%, P = 0.88) were comparable between the two groups. After propensity score matching, the MNT [160 (90-240) µm vs. 110 (60-220) µm, P = 0.048] and neointimal burden [21.4 (8.3-30.1)% vs. 15.4 (5.6-26.3)%, P = 0.044] remained significantly different in the DM compared to the non-DM group. CONCLUSION: DM leads to significant increase in MNT and neointimal burden even with second-generation DES, nevertheless stent strut coverage, ST and NIH characteristics remained comparable among the cohorts at 1-year.

7.
Nat Commun ; 11(1): 5033, 2020 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-33024092

RESUMO

Soaring cases of coronavirus disease (COVID-19) are pummeling the global health system. Overwhelmed health facilities have endeavored to mitigate the pandemic, but mortality of COVID-19 continues to increase. Here, we present a mortality risk prediction model for COVID-19 (MRPMC) that uses patients' clinical data on admission to stratify patients by mortality risk, which enables prediction of physiological deterioration and death up to 20 days in advance. This ensemble model is built using four machine learning methods including Logistic Regression, Support Vector Machine, Gradient Boosted Decision Tree, and Neural Network. We validate MRPMC in an internal validation cohort and two external validation cohorts, where it achieves an AUC of 0.9621 (95% CI: 0.9464-0.9778), 0.9760 (0.9613-0.9906), and 0.9246 (0.8763-0.9729), respectively. This model enables expeditious and accurate mortality risk stratification of patients with COVID-19, and potentially facilitates more responsive health systems that are conducive to high risk COVID-19 patients.


Assuntos
Infecções por Coronavirus/mortalidade , Aprendizado de Máquina , Pandemias , Pneumonia Viral/mortalidade , Idoso , Betacoronavirus , China/epidemiologia , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Redes Neurais de Computação , Medição de Risco , Máquina de Vetores de Suporte
8.
J Hazard Mater ; 404(Pt A): 124015, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-33039827

RESUMO

4-Hydroxyphenylpyruvatedioxygenase (HPPD) is a Fe(II)/Co(II)-dependent enzyme which has become one of the most effective herbicide targets. HPPD inhibitors have been developed as efficient herbicides for resistant weed control. Developing a method for efficient and rapid HPPD inhibitors detection is still challenging. N-n-butyl-4-methylhydrazinecarbothioamide-1,8-naphthalimide (NMN) was synthesized and used to detect Co2+ efficiently with the limit of detection (LOD) of 7.82 nM with a turn-on fluorescence. Herein a novel fluorescent complex, NMN‒Co2+ was employed to determine HPPD inhibitors which performed a turn-off effect in the sensing process based on the competitive coordination between the probe and HPPD with Co2+. The LODs for three commercial triketone HPPD inhibitors (mesotrione, tembotrione and NTBC) were 6.60 nM, 7.37 nM and 10.22 nM with good sensitivity and selectivity. Furthermore, the present probe has potentials to quantitatively detect mesotrione and tembotrione in real samples.

9.
Nat Commun ; 11(1): 5162, 2020 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-33056984

RESUMO

Bioactive natural C-glycosides are rare and chemical C-glycosylation faces challenges while enzymatic C-glycosylation catalyzed by C-glycosyltransferases provides an alternative way. However, only a small number of C-glycosyltransferases have been found, and most of the discovered C-glycosyltransferases prefer to glycosylate phenols with an acyl side chain. Here, a promiscuous C-glycosyltransferase, AbCGT, which is capable of C-glycosylating scaffolds lacking acyl groups, is identified from Aloe barbadensis. Based on the substrate promiscuity of AbCGT, 16 C-glycosides with inhibitory activity against sodium-dependent glucose transporters 2 are chemo-enzymatically synthesized. The C-glycoside 46a shows hypoglycemic activity in diabetic mice and is biosynthesized with a cumulative yield on the 3.95 g L‒1 scale. In addition, the key residues involved in the catalytic selectivity of AbCGT are explored. These findings suggest that AbCGT is a powerful tool in the synthesis of lead compounds for drug discovery and an example for engineering the catalytic selectivity of C-glycosyltransferases.

10.
Artigo em Inglês | MEDLINE | ID: mdl-33038301

RESUMO

PURPOSE: Several studies have investigated risk factors of unfavorable splits associated with sagittal split osteotomies but yielded conflicting information. The purpose of this study is to estimate the frequency of and identify factors associated with unfavorable splits during sagittal split osteotomies (SSOs). MATERIAL AND METHODS: A retrospective cohort study was conducted on patients who underwent orthognathic surgery, including SSOs at our institution from January 2010 to October 2016. The independent variables were mandibular third molar (M3) status, age, gender, and preoperative dentofacial diagnosis. The outcome variable was the effectiveness of the sagittal split resulting in either favorable or an unfavorable split. Data analyses were performed using logistic regression models except in the case of small sample sizes of preoperative dentofacial diagnoses for which the Fisher's exact test was used. RESULTS: A total of 888 patients with an average age of 24.97 ± 5.09 years underwent 1,776 SSOs. Sixteen (0.90%) unilateral unfavorable splits occurred. Unfavorable splits were less common in patients with an M3 present than in patients with the M3 absent. Having an M3 present reduced the chance of an unfavorable split by 69%, adjusted for age and gender; OR (95% CI) = 0.308 (0.103, 0.919); P = .035. The odds of having an unfavorable split were increased by 8.8% for every year of age increase; adjusted OR (95% CI) = 1.088 (1.004, 1.178); P = .038. Based on this estimation, a 45-year-old is 2.3 times more likely to have an unfavorable split compared to a 35-year-old (95% CI:1.041, 5.146), and is 5.4 times more likely to have an unfavorable split compared to a 25-year-old (95% CI:1.083, 26.48). CONCLUSIONS: The presence of a mandibular third molar (M3) was associated with a decreased risk of an unfavorable split, independent of age and gender. There was a significant association between increased age and the incidence of an unfavorable split.

11.
Nat Commun ; 11(1): 5383, 2020 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-33097719

RESUMO

There is a continuous need for designing new and improved synthetic methods aiming at minimizing reaction steps while increasing molecular complexity. In this respect, catalytic, one-pot cascade methodologies constitute an ideal tool for the construction of complex molecules with high chemo-, regio-, and stereoselectivity. Herein, we describe two general and efficient cascade procedures for the synthesis of spiro-fused heterocylces. This transformation combines selective nucleophilic substitution (SN2'), palladium-catalyzed Heck and C-H activation reactions in a cascade manner. The use of allylic ammonium salts and specific Pd catalysts are key to the success of the transformations. The synthetic utility of these methodologies is showcased by the preparation of 48 spiro-fused dihydrobenzofuranes and indolines including a variety of fluorinated derivatives.

12.
Circ Cardiovasc Interv ; 13(9): e009232, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32895005

RESUMO

BACKGROUND: Prognostic impact of residual anatomic disease burden after functionally complete percutaneous coronary intervention (PCI), defined by post-PCI fractional flow reserve (FFR) >0.80 would be a clinically relevant question. The current study evaluated clinical outcomes at 2 years according to residual Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery (SYNTAX) score (RSS) in patients who underwent functionally complete revascularization. METHODS: A total of 1910 patients (2095 revascularized vessels) with post-PCI FFR >0.80 were selected from the International Post-PCI FFR Registry. RSS was defined as the SYNTAX score recalculated after PCI, SYNTAX revascularization index was calculated as 100×(1-RSS/pre-PCI SYNTAX score), and post-PCI FFR was measured after completion of PCI. The primary outcome was target vessel failure (TVF; a composite of cardiac death, target vessel-related myocardial infarction, and clinically driven target vessel revascularization) at 2 years, and risk of TVF was compared according to tertile classification of RSS (0, 1-5, and >5) and post-PCI FFR (≥0.94, 0.87-0.93, and ≤0.86). RESULTS: After PCI, SYNTAX score was changed from 10.0 (Q1-Q3, 7.0-16.0) to 0.0 (Q1-Q3, 0.0-5.0) and FFR changed from 0.70±0.12 to 0.90±0.05. TVF at 2 years occurred in 4.9%, and patients with TVF showed higher pre-PCI SYNTAX score and lower post-PCI FFR than those without. However, there were no significant differences in SYNTAX revascularization index and RSS. The risk of TVF was not different according to tertile of RSS (log-rank P=0.851). Conversely, risk of TVF was different according to tertile of post-PCI FFR (log-rank P=0.009). Multivariable model showed the risk of TVF was significantly associated with post-PCI FFR (hazard ratio, 1.091 [95% CI, 1.032-1.153]; P=0.002) but not with RSS (hazard ratio, 0.969 [95% CI, 0.898-1.045]; P=0.417). CONCLUSIONS: Among patients who underwent functionally complete revascularization, residual anatomic disease burden assessed by RSS was not related with occurrence of TVF at 2 years. These results support the importance of functionally complete revascularization rather than angiographic complete revascularization. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT04012281.

14.
PLoS One ; 15(9): e0238762, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32966282

RESUMO

With the development of modern cities, roads, and landscapes, it is becoming increasingly important for infrastructure such as tunnels to provide an esthetically pleasing experience. In this respect, it is necessary to conduct studies that consider the esthetic design of tunnel portals using esthetics research. Regarding the esthetic evaluation of tunnel portals, this paper fully considers the dynamic visual effect from the driver's perspective. This study combines the use of Blender, SpeedTree Modeler Cinema, Adobe Photoshop CS6, and other software for secondary development. These programs are connected to the driving simulation platform Euro Truck Simulator 2 (which is equipped with a driving simulator) to construct a set of driving simulation tests that enable the esthetic evaluation of a tunnel portal. The Banlun Tunnel on the Funing-Longliu Expressway in Yunnan Province, China, is used as a case study, and four impact factors that vary significantly in esthetic design are included: the linearity, color, greening and texture of the portal. Using an orthogonal experimental design, the influence of the esthetic degree was simulated and evaluated, and the order of sensitivity to esthetic factors of a headwall tunnel portal was sequentially determined as follows: the portal texture exerts the maximum impact on the beauty degree of the headwall portal, followed by the portal greening and the portal color, while the portal linearity exerts the minimum impact. The results show that the developed driving simulation test system can be used to determine the sensitivity of esthetic factors for a tunnel portal and obtain an optimal collocation of esthetic factors on different levels; hence, it provides feedback for use in designing the optimum esthetic tunnel portal. This test system can be used as a reference when conducting future evaluations and studies on tunnel portal esthetics.

15.
BMC Bioinformatics ; 21(1): 377, 2020 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-32883200

RESUMO

BACKGROUND: A large number of experimental studies show that the mutation and regulation of long non-coding RNAs (lncRNAs) are associated with various human diseases. Accurate prediction of lncRNA-disease associations can provide a new perspective for the diagnosis and treatment of diseases. The main function of many lncRNAs is still unclear and using traditional experiments to detect lncRNA-disease associations is time-consuming. RESULTS: In this paper, we develop a novel and effective method for the prediction of lncRNA-disease associations using network feature similarity and gradient boosting (LDNFSGB). In LDNFSGB, we first construct a comprehensive feature vector to effectively extract the global and local information of lncRNAs and diseases through considering the disease semantic similarity (DISSS), the lncRNA function similarity (LNCFS), the lncRNA Gaussian interaction profile kernel similarity (LNCGS), the disease Gaussian interaction profile kernel similarity (DISGS), and the lncRNA-disease interaction (LNCDIS). Particularly, two methods are used to calculate the DISSS (LNCFS) for considering the local and global information of disease semantics (lncRNA functions) respectively. An autoencoder is then used to reduce the dimensionality of the feature vector to obtain the optimal feature parameter from the original feature set. Furthermore, we employ the gradient boosting algorithm to obtain the lncRNA-disease association prediction. CONCLUSIONS: In this study, hold-out, leave-one-out cross-validation, and ten-fold cross-validation methods are implemented on three publicly available datasets to evaluate the performance of LDNFSGB. Extensive experiments show that LDNFSGB dramatically outperforms other state-of-the-art methods. The case studies on six diseases, including cancers and non-cancers, further demonstrate the effectiveness of our method in real-world applications.


Assuntos
Algoritmos , Neoplasias/patologia , RNA Longo não Codificante/metabolismo , Doença de Alzheimer/genética , Doença de Alzheimer/patologia , Área Sob a Curva , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/patologia , Humanos , Neoplasias/genética , RNA Longo não Codificante/genética , Curva ROC
16.
J Agric Food Chem ; 68(39): 10550-10559, 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-32886503

RESUMO

Herbicide safeners enhance herbicide detoxification in crops without affecting target weed sensitivity. To enhance crop tolerance to the toxicity-related stress caused by the herbicide acetochlor (ACT), a new class of substituted phenyl isoxazole derivatives was designed by an intermediate derivatization method as herbicide safeners. Microwave-assisted synthesis was used to prepare the phenyl isoxazole analogues, and all of the structures were confirmed via IR, 1H NMR, 13C NMR, and HRMS. Compound I-1 was further characterized by X-ray diffraction analysis. Bioassay results showed that most of the obtained compounds provided varying degrees of safening against ACT-induced injury by increasing the corn growth recovery, glutathione content, and glutathione S-transferase activity. In particular, compound I-20 showed excellent safener activity against ACT toxicity, comparable to that of the commercial safener benoxacor. Gaussian calculations have been performed and the results indicated that the nucleophilic ability of compound I-20 is higher than that of benoxacor, thus the activity is higher than that of benoxacor. These findings demonstrate that phenyl isoxazole derivatives possess great potential for protective management in cornfields.

17.
Technol Cancer Res Treat ; 19: 1533033820948183, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32940552

RESUMO

BACKGROUND: The present study was designed to investigate the presence or absence of calcification and whether calcification size affect the diagnostic accuracy of ultrasonography (US) and computed tomography (CT) in predicting the benign or malignant nature of thyroid nodules. MATERIAL AND METHODS: From May 2014 to April 2019, 445 patients underwent thyroid US and neck CT before thyroid surgery. In each case, US and CT were retrospectively examined by radiologists. We divided the patients into 3 groups according to the type of calcification: no calcification, microcalcification, and macrocalcification. And macrocalcification group divided into rim calcifications and non-rim calcifications groups. We evaluated the diagnostic accuracy of US and CT for differentiating malignant from benign thyroid nodules using histopathological results as a reference standard. RESULTS: In the overall population, adding CT to US resulted in greater sensitivity, lower specificity, and lower accuracy in the prediction of the benign or malignant nature of nodules. In the group with no calcification, US had a significantly greater accuracy than CT and combined US/CT. In the group with macrocalcification, especially in rim calcifications, adding CT to US resulted in greater sensitivity than US, and CT exhibited greater sensitivity and accuracy than US. CONCLUSION: US is superior to CT for the prediction of the benign or malignant nature of nodules in thyroid lesions according to calcification and CT is also currently not recommended as a routine imaging tool for thyroid nodules. However, the superior sensitivity and accuracy of CT in lesions with macrocalcification especially in rim calcifications may enable CT to play a complementary role in identifying benign and malignant nodules.

18.
JAMA Netw Open ; 3(9): e2018162, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32997128

RESUMO

Importance: The prognostic value of pre-percutaneous coronary intervention (PCI) fractional flow reserve (FFR) may be associated with the post-PCI FFR and their interaction. To correctly interpret the prognostic value of pre-PCI FFR, it is essential to understand to what extent the association of pre-PCI FFR with clinical outcomes is explained by post-PCI FFR. Objective: To investigate the extent to which post-PCI FFR mediates the association of pre-PCI FFR with vessel-related outcomes using an international, multicenter collaboration registry. Design, Setting, and Participants: This cohort study used pooled patient data from 4 international FFR registries. A total of 1488 patients with pre-PCI FFR of 0.80 or less who underwent elective PCI were included. Data collection was conducted from November 2011 to August 2019, and analysis was conducted from September 2019 to July 2020. Main Outcomes and Measures: The primary outcome was target vessel failure (TVF) during 2 years of follow-up. The extent to which post-PCI FFR of less than 0.90 mediated the association of pre-PCI FFR less than 0.75 (vs pre-PCI FFR of 0.75 or greater) with TVF was evaluated using a mediation analysis in a counterfactual framework. Results: Among 1488 patients, the mean (SD) age was 63.5 (9.9) years and 1161 patients (78.0%) were men. The median (interquartile range) pre-PCI and post-PCI FFR were 0.71 (0.62-0.76) and 0.88 (0.83-0.92), respectively. The direct association of low pre-PCI FFR (ie, <0.75) with TVF was significant (odds ratio, 1.81; 95% CI, 1.03-3.17; P = .04), while the mediation by post-PCI FFR level of less than 0.90 was not (indirect association: odds ratio, 1.03; 95% CI, 0.98-1.09; P = .24). In sensitivity analyses using several pre-PCI cutoffs, the mediations by post-PCI FFR were consistently weak. Conclusions and Relevance: In this study, the association of pre-PCI FFR with TVF was not significantly mediated by post-PCI FFR. Poor prognosis due to progressed atherosclerosis, represented as low FFR, may not be reversed by successful PCI that increases FFR. Therefore, the prognostic value of pre-PCI FFR may mainly reflect the global atherosclerotic burden, not the extent of the modifiable epicardial stenosis.

19.
Artigo em Inglês | MEDLINE | ID: mdl-32967863

RESUMO

BACKGROUND: Whether circulating polyunsaturated fatty acid (PUFA) levels are associated with pancreatic cancer risk is uncertain. Mendelian randomization (MR) represents a study design using genetic instruments to better characterize the relationship between exposure and outcome. METHODS: We utilized data from genome-wide association studies within the Pancreatic Cancer Cohort Consortium and Pancreatic Cancer Case-Control Consortium, involving approximately 9,269 cases and 12,530 controls of European descent, to evaluate associations between pancreatic cancer risk and genetically predicted plasma n-6 PUFA levels. Conventional MR analyses were performed using individual-level and summary-level data. RESULTS: Using genetic instruments, we did not find evidence of associations between genetically predicted plasma n-6 PUFA levels and pancreatic cancer risk [estimates per one SD increase in each PUFA-specific weighted genetic score using summary statistics: linoleic acid odds ratio (OR) = 1.00, 95% confidence interval (CI) = 0.98-1.02; arachidonic acid OR = 1.00, 95% CI = 0.99-1.01; and dihomo-gamma-linolenic acid OR = 0.95, 95% CI = 0.87-1.02]. The OR estimates remained virtually unchanged after adjustment for covariates, using individual-level data or summary statistics, or stratification by age and sex. CONCLUSIONS: Our results suggest that variations of genetically determined plasma n-6 PUFA levels are not associated with pancreatic cancer risk. IMPACT: These results suggest that modifying n-6 PUFA levels through food sources or supplementation may not influence risk of pancreatic cancer.

20.
Ann Rheum Dis ; 2020 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-32958509

RESUMO

OBJECTIVES: To determine if plasma microbial small RNAs (sRNAs) are altered in patients with rheumatoid arthritis (RA) compared with control subjects, associated with RA disease-related features, and altered by disease-modifying antirheumatic drugs (DMARDs). METHODS: sRNA sequencing was performed on plasma from 165 patients with RA and 90 matched controls and a separate cohort of 70 patients with RA before and after starting a DMARD. Genome alignments for RA-associated bacteria, representative bacterial and fungal human microbiome genomes and environmental bacteria were performed. Microbial genome counts and individual sRNAs were compared across groups and correlated with disease features. False discovery rate was set at 0.05. RESULTS: Genome counts of Lactobacillus salivarius, Anaerobaculum hydrogeniformans, Staphylococcus epidermidis, Staphylococcus aureus, Paenisporosarcina spp, Facklamia hominis, Sphingobacterium spiritivorum, Lentibacillus amyloliquefaciens, Geobacillus spp, and Pseudomonas fluorescens were significantly decreased in the plasma of RA compared with control subjects. Three microbial transfer RNA-derived sRNAs were increased in RA versus controls and inversely associated with disease activity. Higher total microbial sRNA reads were associated with lower disease activity in RA. Baseline total microbial sRNAs were threefold higher among patients who improved with DMARD versus those who did not but did not change significantly after 6 months of treatment. CONCLUSION: Plasma microbial sRNA composition is altered in RA versus control subjects and associated with some measures of RA disease activity. DMARD treatment does not alter microbial sRNA abundance or composition, but increased abundance of microbial sRNAs at baseline was associated with disease activity improvement at 6 months.

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